tacrolimus and Bacterial-Infections

FK506-binding proteins (FKBPs) contain a domain with peptidyl-prolyl-cis/trans-isomerase (PPIase) activity and bind the immunosuppressive drugs FK506 and rapamycin. FKBPs belong to the immunophilin family and are found in eukaryotes and bacteria.. In this review we describe two major groups of bacterial virulence-associated FKBPs, the trigger factor and Mip-like PPIases. Moreover, we discuss the contribution of host FKBPs in bacterial infection processes.. Since PPIases are regarded as alternative antiinfective drug targets we highlight current research strategies utilizing pipecolinic acid and cycloheximide derivatives as well as substrate based inhibitors.. The current research strategies suggest a beneficial synergism of drug development and basic research. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets.

Topics: Animals; Bacteria; Bacterial Infections; Bacterial Proteins; Cycloheximide; Humans; Peptidylprolyl Isomerase; Sirolimus; Tacrolimus; Tacrolimus Binding Proteins; Virulence Factors

Inverse psoriasis is clinically defined by chronic inflammatory lesions in intertrigineous areas. Colonisation or infection with Candida ssp. or bacteria is common. The disease-related quality of life is significantly reduced especially regarding sexual behavior. After the exclusion of relevant differential diagnoses, therapy should be adapted to the clinical outcome and potential comorbidities. Substances which are efficacious in psoriasis vulgaris are generally efficacious in inverse psoriasis, but have to be used off-label. Controlled clinical studies are only available for topical ascomycin.

Topics: Bacterial Infections; Candidiasis; Diagnosis, Differential; Female; Humans; Male; Off-Label Use; Psoriasis; Superinfection; Tacrolimus

A simplified dosing regimen may improve drug compliance in kidney transplant recipients and long-term graft outcomes. We aimed to identify, appraise, and synthesize the current evidence comparing the relative safety and efficacy of the recently introduced daily versus standard twice-daily tacrolimus administration.. We systematically reviewed all randomized controlled trials and observational studies that compared the outcomes of daily versus twice-daily tacrolimus formulation in kidney transplant recipients. Medline (from 1948 to July week 4 2011), Embase (1980 to 2011 week 31), the Cochrane Library (1991 to June 2011), and conference proceedings were searched without language restriction.. Six randomized controlled trials (n=2499) and 15 observational studies (n=2886) were included in the review. There were no significant differences in biopsy-proven acute rejection (two trials, n=1093; risk ratio [RR; confidence interval (CI)], 1.24 [0.93-1.65]; P=0.15; I=0%), patient survival (three trials, n=1156; RR [CI], 0.99 [0.97-1.02]; P=0.55; I=32%), and graft survival (three trials, n=1156; RR [CI], 0.99 [0.97-1.02]; P=0.67; I=0%) between the two formulations at 12 months. Similar results for acute rejection (five studies, n=391; RR [CI], 0.99 [0.93-1.06]; P=0.84; I=0%) and overall patient survival (two studies, n=218; RR [CI], 1.02 [0.94-1.10]; P=0.62; I=0%) were observed in observational studies.. Once-daily tacrolimus appears to be as effective as twice-daily tacrolimus up to 12 months after kidney transplantation.

Topics: Bacterial Infections; Drug Administration Schedule; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Randomized Controlled Trials as Topic; Tacrolimus

Atopic dermatitis, also known as atopic eczema, is a chronic pruritic skin condition affecting approximately 17.8 million persons in the United States. It can lead to significant morbidity. A simplified version of the U.K. Working Party's Diagnostic Criteria can help make the diagnosis. Asking about the presence and frequency of symptoms can allow physicians to grade the severity of the disease and response to treatment. Management consists of relieving symptoms and lengthening time between flare-ups. Regular, liberal use of emollients is recommended. The primary pharmacologic treatment is topical corticosteroids. Twice-daily or more frequent application has not been shown to be more effective than once-daily application. A maintenance regimen of topical corticosteroids may reduce relapse rates in patients who have recurrent moderate to severe atopic dermatitis. Pimecrolimus and tacrolimus are calcineurin inhibitors that are recommended as second-line treatment for persons with moderate to severe atopic dermatitis and who are at risk of atrophy from topical corticosteroids. Although the U.S. Food and Drug Administration has issued a boxed warning about a possible link between these medications and skin malignancies and lymphoma, studies have not demonstrated a clear link. Topical and oral antibiotics may be used to treat secondary bacterial infections, but are not effective in preventing atopic dermatitis flare-ups. The effectiveness of alternative therapies, such as Chinese herbal preparations, homeopathy, hypnotherapy/biofeedback, and massage therapy, has not been established.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Bacterial Infections; Calcineurin Inhibitors; Cicatrix; Complementary Therapies; Dermatitis, Atopic; Dermatologic Agents; Diagnosis, Differential; Dose-Response Relationship, Drug; Emollients; Histamine Antagonists; Humans; Phototherapy; Pruritus; Skin; Tacrolimus

Chronic otitis externa (COE) remains a frustrating problem for both patient and physician. The end stage of disease, medial fibrosing otitis externa, is very challenging to repair. New and old therapies and promising approaches to the treatment of this often recalcitrant problem are presented in this review.. Tacrolimus, a nonsteroidal immunosuppressant, and fluocinolone acetonide oil 0.01%, a medium-high potency steroid preparation, may offer additional therapeutic options in the struggle against this inflammatory ear canal/skin condition of often unknown cause. Relative potencies of many steroid preparations will be presented along with several treatment strategies for controlling COE. Underlying autoimmune problems such as Sjögren's disease, sarcoidosis, and amyloidosis must be searched and, if present, addressed and treated for resolution of symptoms. Cutting edge therapies, including use of bacteriophages and inflammatory proteases, will also be reviewed.. No single therapy will be successful for every patient with COE. The search for an underlying cause, the removal of all possible irritants to the ear canal skin (e.g. Q-tips, water), debridement, and both topical and occasionally, systemic therapy will control (not cure …) the disease process in the vast majority of patients.

Topics: Anti-Inflammatory Agents; Bacterial Infections; Bacteriophages; Chronic Disease; Debridement; Fluocinolone Acetonide; Humans; Immunosuppressive Agents; Mycoses; Otitis Externa; Peptide Hydrolases; Tacrolimus

Pediatric heart transplantation is a surgical therapy for dilated cardiomyopathy and for complex congenital heart defects with low pulmonary artery resistance. However, it is still discussed as controversial because of uncertain long-term results. We report our experience with pediatric heart transplantation in a heterogeneous population.. Since 1988, 50 heart transplants were performed in 47 patients (30 with dilated cardiomyopathy, 17 with congenital heart disease). Mean age was 9.4 +/- 6.9 years (range, 4 days to 17.9 years). Twenty-three patients had a total of 36 previous operations. Clinical outcome was evaluated retrospectively.. Perioperative mortality was 6% due to primary graft failure. Late mortality (12%) was caused by acute rejection (n = 2), pneumonia (n = 2), intracranial hemorrhage (n = 1), and suicide (n = 1). Mean follow-up was 5.24 +/- 3.6 years. Actuarial 1, 5, and 10 year survival was 86%, 86%, and 80% and improved significantly after 1995 (92% [1 year]; 92% [5 years]). There was no significant difference between patients with dilated or congenital heart disease (1 year: 86% vs 82%; 5 years: 83% vs 74%; 10 years 83% vs 74%; p = 0.62). Three patients with therapy resistant acute or chronic rejection and assisted circulation underwent retransplantation and are alive. Freedom from acute rejection after 5 years was 40% with primary cyclosporine immunosuppression regime and 56% with tacrolimus. Since the introduction of mycophenolate mofetil, freedom from acute rejection increased to 62%. All survivors are at home and in good cardiac condition.. Pediatric heart transplantation is the treatment of choice for end-stage dilated cardiomyopathy as for congenital heart disease with excellent clinical midterm results. It is a valid alternative to reconstructive surgery in borderline patients. However, further follow-up is necessary to evaluate the long-term side effects of immunosuppressants.

Topics: Adolescent; Antiviral Agents; Bacterial Infections; Cardiomyopathy, Dilated; Child; Child, Preschool; Cyclosporine; Cytomegalovirus Infections; Extracorporeal Membrane Oxygenation; Female; Follow-Up Studies; Ganciclovir; Germany; Graft Rejection; Heart Defects, Congenital; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Life Tables; Lymphoma, Non-Hodgkin; Male; Mycophenolic Acid; Pneumonia, Pneumocystis; Postoperative Complications; Reoperation; Retrospective Studies; Survival Analysis; Survival Rate; Tacrolimus; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vascular Resistance; Virus Diseases

Topics: Adrenal Cortex Hormones; Antibodies; Bacterial Infections; Cyclosporine; Humans; Immunosuppressive Agents; In Vitro Techniques; Neutrophils; Tacrolimus

Topics: Animals; Anti-Infective Agents; Antiviral Agents; B-Lymphocytes; Bacterial Infections; Cyclosporine; HIV; Humans; Immunosuppressive Agents; Parasitic Diseases; Polyenes; Sirolimus; T-Lymphocytes; Tacrolimus; Virus Diseases

To evaluate the safety and efficacy of steroid-minimization therapy in liver transplantation (LT) recipients with hepatitis B virus-related diseases in China.. From March 2000 to June 2007, 502 adult LT recipients, mostly with hepatitis B (HBV)-related diseases, were enrolled in our study. Four study groups were setup according to the steroid-minimization protocols: tacrolimus (TAC) with 6 months steroids withdrawal (6M SW), TAC with 3 months SW (3M SW), TAC with 14 days SW (14d SW), and TAC with basiliximab induction and steroids avoidance (Bas SA). All patients were followed up for at least 36 months after LT.. There were no significant differences in the overall 3-year survival rates of the patients and graft, and chronic rejection among the four groups (P = 0.092, P = 0.113 and P = 0.684, respectively). There was also no difference in acute rejection within 12 months after LT (P = 0.514). The 3-year recurrence rates of HBV infection and hepatocellular carcinoma (HCC) after LT were significantly different among all the groups (lowest in TAC/Bas SA group; P = 0.037 and P = 0.029, respectively). The overall incidence of infection was significantly higher in the 6M SW group (62.2% vs 56.1% in 3M SW, 30.5% in 14d SW, 20.5% in Bas SA; P < 0.01). By the end of the 3-year follow-up, more than 90% of the surviving patients could safely receive TAC monotherapy.. Bas SA immunosuppressive protocol can be achieved safely in LT and reduce HBV infection and HCC recurrence and side effects of steroids after LT.

Topics: Adult; Antibodies, Monoclonal; Bacterial Infections; Basiliximab; Carcinoma, Hepatocellular; Chi-Square Distribution; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Hepatitis B, Chronic; Humans; Immunosuppressive Agents; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Neoplasm Recurrence, Local; Recombinant Fusion Proteins; Recurrence; Statistics, Nonparametric; Survival Rate; Tacrolimus

Topics: Antilymphocyte Serum; Azathioprine; Bacterial Infections; Cytomegalovirus Infections; Drug Therapy, Combination; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Liver Transplantation; Muromonab-CD3; Mycoses; Postoperative Complications; Prednisolone; Prospective Studies; Sepsis; Survival Rate; Tacrolimus; Time Factors

In the past, enteric drainage or the omission of induction immunotherapy has been shown to be predictive of suboptimal outcomes of simultaneous pancreas-kidney (SPK) transplantation. We have reassessed the need for bladder drainage and induction immunotherapy to optimize the outcome of SPK transplantation.. One hundred consecutive recipients of SPK transplants who received mycophenolate mofetil and tacrolimus immunosuppression were studied. The first 50 recipients had bladder-drained pancreas allografts and received induction immunotherapy. The results were compared with the next 50 recipients who had enteric-drained pancreas allografts, which included a subgroup (n = 17 patients) who were randomized to receive no induction immunotherapy.. The 1-year actuarial patient, kidney, and pancreas survival rates in the bladder-drainage group were 98.0%, 94.0%, and 94.0%, respectively. The 1-year actuarial patient, kidney, and pancreas survival rates in the enteric-drainage group were 96.8%, 96.8%, and 89.4%, respectively. In the enteric-drainage group, the incidence of rejection at 1 year was 6.1% in recipients who received induction therapy versus 23.5% in recipients who did not receive induction therapy. The average number of readmissions per recipient was 1.8 in the bladder-drainage group versus 0.9 in the enteric-drainage group.. Primary enteric drainage of the pancreas allograft in recipients of SPK transplantation is the preferred surgical technique in the tacrolimus/mycophenolate mofetil era.

Topics: Adult; Bacterial Infections; Drainage; Female; Graft Rejection; Graft Survival; Humans; Hypertension, Renal; Immunosuppressive Agents; Incidence; Intestines; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Pancreas Transplantation; Patient Readmission; Postoperative Complications; Survival Analysis; Tacrolimus; Treatment Outcome; Urinary Bladder

Tacrolimus (FK506) has recently become available clinically as an alternative to cyclosporine-based immunosuppression. This study reports the middle-term results of a prospective, randomized trial that compared FK506 with cyclosporine-based immunosuppression in heart transplant recipients.. Twenty-five consecutive patients were randomized at a 2:1 ratio into two groups, one of which received FK506 (15 patients), the other cyclosporine (10 patients). Both groups received similar concomitant immunosuppression. The patients were followed up for 12 months. The following outcome parameters were analyzed: survival, rejection and infection rate, lymphocyte subsets, new-onset diabetes, renal and hepatic function, hypertension, right-sided heart catheterization data, graft coronary artery disease, and neurologic side effects.. The mortality rate (two patients) in the FK506 group was 13% versus 0% in the cyclosporine group (p = NS). The two deaths were the consequences of early infections and higher doses of FK506. From the outset, the FK506 group presented a lower prevalence of acute rejection, a lower requirement for rejection treatments and a higher incidence of infections. Accordingly, we reduced overall immunosuppression for the last seven patients in the FK506 group; the decrease in FK506 and prednisone dosage led to a decrease in the early infection rate without an increase in the rejection rate. There was no difference between the two groups in diabetes incidence, renal and hepatic function, right-sided heart catheterization data, or coronary angiograms. Hypertension was less frequent and milder in the FK506 group.. This experience suggests that FK506 can be safely used in heart transplantation. It can decrease the frequency of rejection episodes. Low-dose administration allows a lower infection rate without an increase in rejection. With a protocol of delayed starting and low dosing, side effects such as renal toxicity, hypertension, and neurologic toxicity seem to be unlikely. Further studies are needed to establish the exact dosage and therapeutic levels of the drug.

Topics: Acute Disease; Bacterial Infections; Cardiac Catheterization; Coronary Disease; Cyclosporine; Diabetes Mellitus; Female; Follow-Up Studies; Graft Rejection; Heart Transplantation; Humans; Hypertension; Immunosuppressive Agents; Incidence; Kidney; Liver; Lymphocyte Subsets; Male; Middle Aged; Nervous System; Prevalence; Prospective Studies; Survival Rate; Tacrolimus; Treatment Outcome

Topics: Bacterial Infections; Blood Pressure; Cadaver; Cyclosporine; Drug Monitoring; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Kidney Transplantation; Male; Mycoses; Patient Selection; Postoperative Complications; Prednisolone; Tacrolimus; Time Factors; Tissue Donors; Virus Diseases

Topics: Adult; Bacterial Infections; Cyclosporine; Female; Follow-Up Studies; Humans; Liver Transplantation; Male; Mycoses; Postoperative Complications; Tacrolimus; Virus Diseases

Topics: Bacterial Infections; Child; Humans; Liver Transplantation; Mycoses; Retrospective Studies; Tacrolimus; Virus Diseases

Bloodstream infection (BSI) is a common complication after living-donor liver transplantation (LDLT). Some patients develop recurrent BSIs. We evaluated the impacts of early recurrent BSIs (ER-BSIs) on outcomes in LDLT recipients. LDLT cases between 2008 and 2016 were included. Early BSI (E-BSI) was defined as a BSI event that occurred within 2 months after LDLT. ER-BSIs were defined as new-onset BSIs within 2 months due to another pathogen at a ≥ 48-h interval or a relapse of BSIs by the same pathogen at a ≥ 1-week interval, with negative cultures in between. The primary objective was evaluating the all-cause mortality of each group of LDLT recipients (90 days and 1 year). The secondary objectives were analyzing associated factors of each all-cause mortality and risk factors for early single BSI and ER-BSI. Among 727 LDLT recipients, 108 patients experienced 149 events of E-BSI with 170 isolated pathogens. Twenty-eight patients (25.9%, 28/108) experienced ER-BSI. The 1-year survival rates of patients without BSI, with early single BSI event, and with ER-BSIs were 92.4%, 81.3%, and 28.6%, respectively. ER-BSI was the most significant risk factor for 1-year mortality (adjusted HR = 5.31; 95% CI = 2.27-12.40). Intra-abdominal and/or biliary complications and early allograft dysfunction were risk factors for both early single BSI and ER-BSI. Interestingly, longer cold ischemic time and recipient operative time were associated with ER-BSI. LDLT recipients with ER-BSI showed very low survival rates accompanied by intra-abdominal complications. Clinicians should prevent BSI recurrence by being aware of intra-abdominal complications.

Topics: Anti-Bacterial Agents; Bacteremia; Bacteria; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Immunosuppressive Agents; Liver Transplantation; Living Donors; Recurrence; Tacrolimus; Treatment Outcome

AR is lower in pKTx recipients on Tac vs CsA. Data comparing infection outcomes for children treated with these agents are limited. We retrospectively studied infection outcomes in 96 pKTx recipients on a RDP. PS, DCGS, AR, and infection-free survival were assessed using Kaplan-Meier/log-rank tests and proportional hazards models. There were no differences in 1-year PS, DCGS, or AR between Tac and CsA recipients. After adjusting for AR, the hazard of CMV viremia was 4.0 times higher (95%CI: 1.04, 15.5; P = .044) and that of BK viremia was 3.8 times higher (95%CI: 1.5, 10.2; P = .007) in Tac recipients. The incidence of EBV viremia was similar between the groups (P = .56). PostTx lymphoproliferative disease was only observed in Tac recipients (3%). There was no difference in the incidence of pneumonia, urinary tract, or Clostridium difficile infections between Tac and CsA recipients. Among KTx recipients on RDP, the hazards of CMV and BK viremia within 1 year post-KTx were significantly higher in Tac recipients compared to CsA. Regular assessment for infections and lower Tac trough levels may be warranted in Tac recipients.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Cyclosporine; Drug Administration Schedule; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Kaplan-Meier Estimate; Kidney Transplantation; Male; Postoperative Complications; Prednisone; Proportional Hazards Models; Retrospective Studies; Tacrolimus; Treatment Outcome; Virus Diseases

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited response to currently available therapies. Alveolar type II (ATII) cells act as progenitor cells in the adult lung, contributing to alveolar repair during pulmonary injury. However, in IPF, ATII cells die and are replaced by fibroblasts and myofibroblasts. In previous preclinical studies, we demonstrated that ATII-cell intratracheal transplantation was able to reduce pulmonary fibrosis. The main objective of this study was to investigate the safety and tolerability of ATII-cell intratracheal transplantation in patients with IPF.. We enrolled 16 patients with moderate and progressive IPF who underwent ATII-cell intratracheal transplantation through fiberoptic bronchoscopy. We evaluated the safety and tolerability of ATII-cell transplantation by assessing the emergent adverse side effects that appeared within 12 months. Moreover, pulmonary function, respiratory symptoms, and disease extent during 12 months of follow-up were evaluated.. No significant adverse events were associated with the ATII-cell intratracheal transplantation. After 12 months of follow-up, there was no deterioration in pulmonary function, respiratory symptoms, or disease extent.. Our results support the hypothesis that ATII-cell intratracheal transplantation is safe and well tolerated in patients with IPF. This study opens the door to designing a clinical trial to elucidate the potential beneficial effects of ATII-cell therapy in IPF.

Topics: Adrenal Cortex Hormones; Aged; Alveolar Epithelial Cells; Anti-Infective Agents; Bacterial Infections; Bronchoscopy; Cell Transplantation; Disease Progression; Female; Forced Expiratory Volume; Ganciclovir; Graft Rejection; Humans; Idiopathic Pulmonary Fibrosis; Immunosuppressive Agents; Leucovorin; Male; Middle Aged; Mycophenolic Acid; Mycoses; Nystatin; Pulmonary Diffusing Capacity; Tacrolimus; Trachea; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Valganciclovir; Virus Diseases; Vital Capacity; Walk Test

BACKGROUND Mycophenolic acid (MPA) prodrugs are anti-proliferative immunosuppressive agents commonly used after organ transplantation. Although they are generally well tolerated by patients, adverse effects may occur. It is postulated that MPA metabolites could also contribute to these adverse effects. MATERIAL AND METHODS The objective of this study was the assessment of concentrations of total MPA and its metabolites, phenyl glucuronide (MPAG), acyl glucuronide (AcMPAG) and glucoside (GluMPA), using liquid chromatography combined with mass spectrometry (LC/MS/MS) in two groups: kidney transplant recipients and liver transplant patients. Associations of MPA and its metabolites with adverse effects were analyzed. RESULTS The study group consisted of 211 recipients of liver or kidney transplants who received immunosuppressive therapy, including MPA prodrugs. Multivariant analysis showed a positive influence of MPA on gastroenterotoxicity in kidney transplant recipients. In liver patients, gastroenterotoxicity was associated with lower MPAG concentrations. A positive influence of AcMPAG on bacterial infections in liver transplant patients was observed. In liver transplant recipients, a positive influence of MPA and a negative influence of GluMPA levels on the PLT count were revealed. MPA and its metabolites did not influence the hemoglobin levels in both groups. There were no significant relationships among MPA, its metabolites and WBC counts. CONCLUSIONS In kidney transplant recipients, total MPA trough concentration is associated with gastroenterotoxicity and its monitoring could have important role in management of gastrointestinal complications. The quantification of AcMPAG in liver recipients receiving MPA may be helpful in avoiding bacterial infections. GluMPA seems to have a toxic effect on thrombopoiesis.

Topics: Adult; Bacterial Infections; Cyclosporine; Female; Glucosides; Glucuronides; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Transplant Recipients

Little information is available regarding the impact of cytochrome P450 (CYP) 3A5 on the metabolism of TAC in infant LTx. Therefore, the CYP3A5 genotype of Chinese pediatric recipients (intestine) as well as donors (graft liver) was performed for the purpose of establishing an optimal dosage regimen in children. Sixty-four patients were divided according to CYP3A5 genotype (expression of *1 allele: EX and NEX) for each recipient (R) and donor (D), EX-R/EX-D (n = 21), EX-R/NEX-D (n = 8), NEX-R/EX-D (n = 8) and NEX-R/NEX-D (n = 27). Results indicated that initial TAC daily dose requirement was higher among EX-R/EX-D children compared with those who did not express CYP3A5 (0.28 ± 0.10 vs. 0.19 ± 0.08 mg/kg/day, p < 0.01). CYP3A5 expression contributed an overall of 38.35% to its C/D ratios, and graft liver was a key determinant. Additionally, the EX-R/EX-D group showed significantly higher incidence of infectious complications, lower immune response and was an independent risk factor for the development of infections (odds ratio 3.86, p = 0.025). Donor CYP3A5 expression partially explains TAC dose requirement, the effect of CYP3A5 variation may influence clinical outcomes; therefore, monitoring immune response may be important for preventing risks associated with under- and over-immunosuppression.

Topics: Bacterial Infections; Child, Preschool; China; Cytochrome P-450 CYP3A; Female; Genotype; Humans; Immunosuppressive Agents; Infant; Liver Failure; Liver Transplantation; Male; Pharmacogenetics; Postoperative Complications; Regression Analysis; Risk Factors; Tacrolimus; Treatment Outcome; Virus Diseases

The aim of this study is to evaluate whether the combination of the ImmuKnow assay (IMK) and cytochrome P450 3A5 (CYP3A5) genotype assay is useful for identifying the risk of morbidity and mortality in living donor liver transplantation (LDLT) patients, and also to investigate the optimal cutoff value of IMK level of immune status.. Sixty six LDLT patients, who were randomly screened by using IMK between March 2002 and June 2011, were divided into 2 groups: patients in whom at least 1 IMK value was <175 ng/mL (Group A, n=16) and patients in whom all IMK values were >175 ng/mL (Group B, n=50). Both donors and recipients were evaluated for the CYP3A5 genotype.. The frequencies of cytomegalovirus and bacterial infection in Group A were significantly higher than those in Group B (P<0.001). The short term mortality was 4 (25.0%) in Group A and none in Group B, and the IMK level in all four cases became <100 ng/mL at least one time before death. The rate of CYP3A5*1 allele (expressors) among recipients was significantly higher in Group A than in Group B (63.6% vs. 22.2%, P=0.0147). The rates of CMV infection and bacterial infection, and the IMK levels was significantly higher in recipients with expressors (p=0.0216, p=0.0332, and p=0.0433, respectively).. The combination of the IMK and CYP3A5 genotype assay is useful for monitoring immune status after LDLT, and the IMK level <100 ng/ml might be the critical level to make a recovery from the severe immunesupressive condition.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Child; Child, Preschool; Cytochrome P-450 CYP3A; Cytomegalovirus Infections; Female; Genotype; Humans; Immunoassay; Immunosuppressive Agents; Infant; Infections; Liver Transplantation; Living Donors; Male; Middle Aged; Morbidity; Polymorphism, Single Nucleotide; Risk Factors; Tacrolimus; Young Adult

To investigate the factors in association with colorectal disorders in adult renal transplant recipients.. A retrospective cohort study was carried out with clinical, microbiological and management data regarding diarrhea in 513 renal transplant recipients from Jan. 2007 to Dec. 2012.. Of the 513 patients, 118(23.00%) with no history of ulcerative colitis, were found to have diarrhea after kidney transplantation. In the 118 patients, diarrhea was probably caused by administration of immunosuppressive agents in 65 cases (55.08%), in 30 cases (25.42%) diarrhea was antibiotics associated, and in 23 cases (19.49%) it was due to infections, including bacterial, fungal and viral infections. Diarrhea occurred soon after transplantation in most cases. Of the 118 patients, the symptom of diarrhea occurred in the first 1 month in 84 cases (71.19%), and in the next 5 months in 16 cases (13.56%), and the other 18 cases (15.05%) occurred after 180 days after transplantation. Of the 118 patients, 84 cases (71.19%) were relieved or cured after proper diets, the symptomatic therapy or the adjust meat of the doses of immunosuppressive agents: 18 cases (15.25%) needed to use or adjust the antibiotics , 16 cases (13.56%) had to stop mycophenolate mofetil and convert to other drugs.. Immunosuppressive agents, antibiotics and infection are the common causes of diarrhea after kidney transplantation. The outcome is good with appropriate conservative management.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Child; Cyclosporine; Cytomegalovirus Infections; Diarrhea; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Mycoses; Retrospective Studies; Tacrolimus; Young Adult

Despite significant improvements in renal transplantation (RTX), certain basic issues remain unresolved such as the routine use of perioperative antibiotic prophylaxis (PAP). To address the need for PAP, we retrospectively evaluated the clinical course of 349 consecutive RTX patients who did not receive any PAP except for Bactrim. Of the 349 transplant recipients, 77% received induction therapy with low-dose rabbit antithymocyte globulin (rATG) and the others were treated with basiliximab. All patients received triple immunosuppression with tacrolimus, mycophenolic acid, and prednisone. Seven patients (2%) developed wound infections. Wound infections were more common in obese and older patients. All wound infections were superficial and responded well to wound drainage and outpatient antibiotic therapy. Six patients (1.7%) experienced a urinary tract infection (UTI) within the first postoperative month. UTIs were more common in the patient with ureteral stent compared to nonstented patients (11.4% vs 0.3%, P<.001). No patient or graft was lost due to perioperative bacterial infections (PBI). Our study shows that despite many predisposing factors, PBI are rare following RTX even in the absence of PAP. Therefore, in order to avoid emergence of multiantibiotic-resistant pathogens, excessive costs, and antibiotic-related adverse events, we suggest that PAP should be used only in selected circumstances such as in recipients older than 60 or when the body mass index is greater than 35.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Antibodies, Monoclonal; Antilymphocyte Serum; Bacterial Infections; Basiliximab; Body Mass Index; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisone; Rabbits; Recombinant Fusion Proteins; Retrospective Studies; Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

There is an urgent need for the design and development of new and selective drugs for the treatment of malaria and bacterial infections as these pathogens are developing resistance to presently available therapies. Malaria is a life threatening disease in many countries and responsible for almost one million deaths annually. In particular, drug-resistant malarial parasites are hindering effective control of malaria and prompting to find novel druggable targets and develop compounds with mechanism of action different from the conventional drugs. In this quest, efforts were made to determine three-dimensional structures of Plasmodium falciparum and Plasmodium vivax FK506 binding proteins which bind the macrolides (FK506 and rapamycin) and also demonstrate peptidylprolyl cis-trans isomerase activity in a similar manner as human FKBP12. Previous studies revealed that the immunosuppressive drug FK506 exhibits potential anti-malarial activity by binding FK506 binding domains (FKBD). This review focuses on three different types of FK506 binding proteins/domains in pathogens, their structural characteristics and biological roles. Binding ability of these proteins with the macrolides has opened new possibilities to develop selective inhibitors for these novel targets to combat the life threatening infections.

Topics: Bacterial Infections; Drug Delivery Systems; Humans; Immunosuppressive Agents; Malaria; Sirolimus; Tacrolimus; Tacrolimus Binding Proteins

Perianal fistulas are a chronic, debilitating disease that requires lifelong monitoring and, potentially, lifelong treatment. Lesions are characterized by ulcerations with draining fistulous tracts around the anal region. Most dogs experience significant pain and discomfort with this condition. Bacterial infections are a frequent secondary problem. Definitive diagnosis is based on clinical signs, signalment, history, and a thorough examination. The most successful treatment is immunomodulatory therapy (cyclosporine with or without ketoconazole and topical tacrolimus). Perianal fistulas can be difficult to treat, frustrating both veterinarians and owners.

Topics: Animals; Bacterial Infections; Dog Diseases; Dogs; Immunosuppressive Agents; Intestinal Fistula; Perianal Glands; Recurrence; Tacrolimus; Treatment Outcome

Neutropenic episodes in kidney transplant patients are poorly characterized. In this retrospective study, neutropenia was experienced by 112/395 patients (28%) during the first year posttransplant. The only factor found to be significantly associated with the occurrence of neutropenia was combined tacrolimus-mycophenolate therapy (p < 0.001). Neutropenic patients experienced more bacterial infections (43% vs. 32%, p = 0.04). Grade of neutropenia correlated with the global risk of infection. Discontinuation of mycophenolic acid (MPA) due to neutropenia was associated with an increased incidence of acute rejection (odds ratios per day 1.11, 95% confidence intervals 1.02-1.22) but not with reduced renal function at 1 year. The time from onset of neutropenia to MPA discontinuation correlated with the duration of neutropenia. Granulocyte colony-stimulating factor (G-CSF) administration was safe and effective in severely neutropenic kidney graft recipients, with absolute neutrophil count >1000/microL achieved in a mean of 1.5+/-0.5 days. Neutropenia is an important and frequent laboratory finding that may exert a significant influence on outcomes in kidney transplantation. As well as leading to an increased incidence of infection, it is associated with a higher rate of allograft rejection if MPA is discontinued for >6 days (p = 0.02). G-CSF accelerates recovery of neutropenia and may be a good therapeutic alternative for severely neutropenic patients.

Topics: Adult; Aged; Bacterial Infections; Drug Therapy, Combination; Female; Graft Rejection; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Neutropenia; Retrospective Studies; Risk Factors; Tacrolimus

Haemophagocytic syndrome (HPS) is known as a relatively rare complication in autoimmune diseases. Here we analysed the clinical features of HPS in patients with systemic autoimmune diseases.. One thousand and fourteen patients with systemic autoimmune diseases admitted to Hokkaido University Hospital from 1997 to 2007 were recruited [350 SLE, 136 RA, 98 polymyositis/dermatomyositis (PM/DM), 88 SSc, 91 vasculitis syndrome, 37 primary SS, 26 adult onset Still's disease (AOSD) and 188 other diseases]. Clinical features and treatment outcomes were retrospectively analysed.. Thirty cases (3.0%) fulfilled HPS criteria (progressive cytopenia in two or more lineages and haemophagocytosis in reticuloendothelial systems). Underlying diseases were SLE (18), RA (2), PM/DM (2), SSc (2), vasculitis (1), SS (2) and AOSD (3). Nineteen patients were diagnosed as having autoimmune-associated HPS, eight infection-associated, one drug-induced and one developed HPS after haematopoietic stem cell transplantation. For the treatment of HPS, high-dose corticosteroid monotherapy was given in 26 cases, being effective in 12 (46%). Ten out of 15 patients with corticosteroid-resistant autoimmune-associated HPS were treated with CsA, cyclophosphamide or tacrolimus, leading to the remission in 80%. The overall mortality rate was 20%. Multivariate analysis showed that the presence of infections and CRP level >50 mg/l on HPS related with poor prognosis.. The prevalence of HPS among in-hospital patients with systemic autoimmunity is not ignorable. Administration of immunosuppressants was effective in cases with autoimmune-associated HPS, whereas prognosis was poor in infection-associated HPS.

Topics: Adult; Aged; Autoimmune Diseases; Bacterial Infections; Cyclophosphamide; Cyclosporine; Glucocorticoids; Humans; Immunosuppressive Agents; Lymphohistiocytosis, Hemophagocytic; Middle Aged; Prognosis; Retrospective Studies; Tacrolimus; Virus Diseases; Young Adult

Topics: Adrenal Cortex Hormones; Bacterial Infections; Calcineurin Inhibitors; Child; Cyclosporine; Humans; Immunosuppressive Agents; Opportunistic Infections; Tacrolimus

Studies of renal transplantation utilizing trough plasma level monitoring of mycophenolic acid (MPA) have shown inconsistent associations with toxicity and rejection. In this study, 5600 12-h trough MPA samples from 121 renal transplant recipients immunosuppressed with mycophenolate mofetil (MMF) and tacrolimus in a steroid sparing protocol (steroids for 7 days only) were sequentially analyzed. Higher MPA levels were associated with lower hemoglobin concentrations and anemia (hemoglobin <10 g/dL). Similarly, higher MPA levels were associated with lower total white cell counts and an increased incidence of leucopenia (total white cell count <4.0 x 10(9)/L). Hypoalbuminemia and renal impairment were also associated with hemotoxicity. MMF-associated diarrhea and viral infection were associated with higher MPA levels. Conversely, biopsy-proven acute rejection within the first month post-transplantation was associated with lower MPA levels. Anti-CD25 antibody induction was also associated with reduced rejection rates. No association was seen between MPA levels and platelet count, thrombocytopenia or bacterial infection. An MPA level of 1.60 mg/L early post-transplantation best discriminated patients with and without rejection, and an MPA level of 2.75 mg/L best discriminated patients with and without toxicity later post-transplantation.

Topics: Adult; Bacterial Infections; Bone Marrow; Diarrhea; Dose-Response Relationship, Drug; Drug Monitoring; Female; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Leukocyte Count; Leukopenia; Male; Middle Aged; Monitoring, Physiologic; Mycophenolic Acid; Platelet Count; Tacrolimus; Thrombocytopenia; Virus Diseases

Pediatric heart transplantation is entering its third decade, allowing for the first time an analysis of a large group of true long-term survivors, specifically children who have survived > or =10 years post-transplantation.. Fifty-two patients < or =18 years, who had undergone heart transplantation at Stanford between August 1974 and June 1993 and survived > or =10 years, were retrospectively reviewed.. Forty (77%) patients are currently alive. Thirteen survived >15 years and 5 >20 years (the longest being 26 years). Actuarial survival was 79.4% at 14 years and 53.1% at 20 years. Cardiomyopathy was the reason for transplantation in 71% and congenital heart disease (CHD) in 29%. At last evaluation, 71% were on a cyclosporine-based regimen and 23% a tacrolimus-based regimen; 33% were steroid-free. Twenty-seven percent were totally free from treatable rejection, 44% developed serious infections, 69% were receiving anti-hypertensives, and 8% required renal transplantation. Neoplasms occurred in 23%, graft coronary artery disease (CAD) in 31%, and 15% required re-transplantation. Of the 12 deaths, CAD was the most common cause (n = 4), followed by non-specific late graft failure (n = 3), infection (n = 2), rejection (n = 1), non-lymphoid cancer (n = 1) and lymphoid cancer (n = 1). Physical rehabilitation and return to normal lifestyle has been nearly 100%.. Heart transplantation in pediatric patients is compatible with true long-term survival with a growing cohort of children approaching their second and third decades. The gradual constant-phase decrease in survival noted in earlier studies appears to be continuing. Rejection and infection are low but persistent risks after the first years. Graft CAD and non-specific late graft dysfunction are the leading causes of death after 10 years. Rehabilitation is excellent.

Topics: Actuarial Analysis; Adolescent; Bacterial Infections; Cardiomyopathies; Child; Child, Preschool; Coronary Artery Disease; Cyclosporine; Female; Graft Rejection; Heart Defects, Congenital; Heart Transplantation; Humans; Immunosuppressive Agents; Infant; Lymphoproliferative Disorders; Male; Reoperation; Retrospective Studies; Survival Analysis; Survivors; Tacrolimus

Liver injury is a common complication in allogeneic hematopoietic stem cell transplantation. Its major causes comprise graft-versus-host disease (GVHD), infection, and toxicities of preparative regimens and immunosuppressants; however, we have little information on liver injuries after reduced intensity cord blood transplantation (RICBT). We reviewed medical records of 104 recipients who underwent RICBT between March 2002 and May 2004 at Toranomon Hospital. Preparative regimen and GVHD prophylaxis comprised fludarabine/melphalan/total body irradiation and cyclosporine or tacrolimus. We assessed the etiology of liver injuries based on the clinical presentation, laboratory results, comorbid events, and imaging studies in 85 patients who achieved primary engraftment. The severity of liver dysfunction was assessed according to the National Cancer Institute Common Toxicity Criteria version 2.0. Hyperbilirubinemia was graded according to a report by Hogan et al (Blood. 2004;103:78-84). Moderate to very severe liver injuries were observed in 36 patients. Their causes included cholestatic liver disease (CLD) related to GVHD or sepsis (n = 15), GVHD (n = 7), cholangitis lenta (n = 5), and others (n = 9). Median onsets of CLD, GVHD, and cholangitis lenta were days 37, 40, and 22, respectively. Frequencies of grade 3-4 alanine aminotransferase elevation were comparable across the 3 types of hepatic injuries. Serum gamma-glutamil transpeptidase was not elevated in any patients with cholangitis lenta, whereas 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3-4 gamma-glutamil transpeptidase elevation. Multivariate analysis identified 2 risk factors for hyperbilirubinemia; grade II-IV acute GVHD (relative risk, 2.23; 95% confidential interval, 1.11-4.47; P = .024) and blood stream infection (relative risk, 3.77; 95% confidential interval, 1.91-7.44; P = .00013). In conclusion, the present study has demonstrated that the hepatic injuries are significant problems after RICBT, and that GVHD and blood stream infection contribute to their pathogenesis.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Busulfan; Chemical and Drug Induced Liver Injury; Cholangitis; Cord Blood Stem Cell Transplantation; Cyclosporine; Female; Hematologic Diseases; Hematologic Neoplasms; Hepatic Veno-Occlusive Disease; Humans; Hyperbilirubinemia; Immunosuppressive Agents; Incidence; Infant, Newborn; Liver Diseases; Liver Function Tests; Male; Melphalan; Middle Aged; Postoperative Complications; Risk Factors; Tacrolimus; Tissue Donors; Transplantation Conditioning; Vidarabine; Whole-Body Irradiation

Transgenic mice expressing an inducible suicide gene, which allows systemic and reversible elimination of macrophages, were developed. A macrophage-specific c-fms promoter was used to express enhanced green fluorescent protein and a drug-inducible suicide gene that leads to Fas-mediated apoptosis in resting and cycling cells of the macrophage lineage. Transgenic mice were fertile, of normal weight, and showed no abnormal phenotype before drug exposure. The transgene was expressed constitutively in macrophages and dendritic cells (DC) but not significantly in T cells or B cells. Induction of the suicide gene led to depletion of 70-95% of macrophages and DC in nearly all tissues examined. Depletion reduced the ability to clear bacteria from the blood and led to increased bacterial growth in the liver. Depleted mice displayed several abnormalities, including splenomegaly, lymphadenopathy, thymic atrophy, extramedullary hematopoiesis, and development of peritoneal adhesions. This new, transgenic line will be useful in investigating the role of macrophages and DC.

Topics: Animals; Apoptosis; Bacterial Infections; Cell Count; Cells, Cultured; Dendritic Cells; Dimerization; Disease Models, Animal; fas Receptor; Genes, Transgenic, Suicide; Green Fluorescent Proteins; Immunity, Cellular; Luminescent Proteins; Macrophages; Mice; Mice, Inbred C57BL; Mice, Transgenic; Promoter Regions, Genetic; Receptor, Macrophage Colony-Stimulating Factor; Receptors, Nerve Growth Factor; Tacrolimus; Tacrolimus Binding Proteins

Complement factor H (FH) deficiency is one of the causes of atypical hemolytic uremic syndrome (HUS). Most patients with FH deficiency associated HUS progress to end-stage renal disease despite plasma therapy. Moreover, the disease invariably recurs in the graft kidney and causes graft failure. We confirmed FH deficiency in a 30-month-old boy with recurrent HUS of 2 years duration, and attempted an auxiliary partial orthotopic liver transplantation (APOLT) to overcome the sustained intractable dependency on plasma therapy. APOLT restored the plasma FH level, without HUS recurrence, for 7 months. However, thereafter he suffered from serious infectious complications associated with immunosuppression and finally died 11 months after APOLT. In conclusion, although APOLT showed clinical and laboratory improvement for some period in this patient, the final fatal outcome suggests that liver transplantation should be cautiously applied to patients with HUS associated with FH deficiency.

Topics: Bacterial Infections; Blotting, Western; Child, Preschool; Complement Factor H; Epstein-Barr Virus Infections; Fatal Outcome; Hemolytic-Uremic Syndrome; Humans; Immunocompromised Host; Immunosuppressive Agents; Infant; Liver Failure; Liver Transplantation; Lymphoproliferative Disorders; Male; Tacrolimus

The metabolism of tacrolimus is influenced by several medications when they are given concurrently. We report the interaction between tacrolimus and chloramphenicol in a renal transplant recipient.. An adolescent with vancomycin-resistant Enterococcus was given standard doses of chloramphenicol. Tacrolimus trough levels increased, and the dose was adjusted to maintain the target trough level. Pharmacokinetic studies were obtained during chloramphenicol administration and 14 days after its discontinuation.. Toxic levels of tacrolimus were seen on the second day of chloramphenicol administration, requiring an 83% reduction in the tacrolimus dose. The dose-adjusted area under the curve value for tacrolimus was 7.5-fold greater while the patient was on chloramphenicol. These data are consistent with inhibition of tacrolimus clearance by chloramphenicol. Chloramphenicol interferes with tacrolimus metabolism. Careful monitoring of tacrolimus trough levels during concomitant chloramphenicol therapy is recommended to avoid toxicity.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Chloramphenicol; Dose-Response Relationship, Drug; Drug Interactions; Enterococcus; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Peritonitis; Postoperative Complications; Tacrolimus

Major bacterial infections and the predictors of early (within 100 days of transplantation) versus late onset (after 100 days post-transplant) bacterial infections were prospectively assessed in 130 consecutive liver transplant recipients receiving tacrolimus (FK506) as primary immunosuppression. The median follow-up period was 38 months. Overall, 35% (45/130) of the patients developed 67 episodes of major bacterial infections (0.52 episodes/patient). Sixty-three percent of the major bacterial infections occurred early, and 37% occurred in the late post-transplant period. Eighty-four percent of the abdominal infections occurred early, whereas 38% of the cases of pneumonia, 60% of the cases of primary bacteremia, and 50% of the biliary infections occurred late. By logistic regression analysis, portal vein thrombosis was the most significant independent risk factor for early-onset major bacterial infection (odds ratio 4.1; 95% CI 1.4-12.2), and recurrent hepatitis C was the most significant independent predictor of late-onset major bacterial infections (odds ratio 6.21; 95% CI 1.9-20.2). Thus, sources and risk factors differ for early versus late-onset bacterial infections after liver transplantation. Knowledge of the differences in the potential sources, the pathogens, and the predictors of early versus late-onset bacterial infections can be valuable in the evaluation and empiric treatment of liver transplant recipients with bacterial infections.

Topics: Adult; Aged; Bacterial Infections; Humans; Immunosuppressive Agents; Liver Transplantation; Middle Aged; Risk Factors; Tacrolimus

A retrospective cohort study was conducted to determine the incidence of major infectious complications after orthotopic liver transplantation and to compare outcomes in patients receiving either cyclosporine (CsA) or FK506 (tacrolimus) as primary immunosuppression. Of 133 transplants performed in 118 patients, 124 transplant episodes were evaluated. Cytomegalovirus (CMV) infection (INF) and disease (DIS), deep fungal infection (DFI), and intraabdominal bacterial infections (IAI) were catalogued. The overall incidences of major infectious outcomes were: CMV INF = 33%; CMV DIS = 19%; DFI = 15%; and IAI = 25%. Cox proportional hazard analysis identified donor seropositivity, OKT3 as secondary immunosuppression and initial intensive care unit (ICU) duration as risk factors for CMV INF and DIS in the overall population. Fungal colonization was the dominant risk factor associated with deep fungal infection. A choledochojejunostomy anastomosis, the number of cellular blood products transfused at the time of transplantation surgery, and prior CMV INF were independent risk factors for both fungal colonization and deep infection. The single risk factor identified for intraabdominal bacterial infections was the number of cellular blood products transfused at the time of surgery. In the Cox proportional hazards model the relative risk (RR) for each category of infection was lower in the FK506 group (CMV: RR = .87, 95% confidence interval [C.I.] = [.32-2.4]; DFI: .58 [.13-2.6]; IAI: .51 [.15-1.7]), but the effect was not statistically significant. Survival was similar in patients receiving FK506 or CsA. CMV INF and DFI were independent predictors of death for all patients. Risk factors identified for CMV INF and DIS support the findings of others. Higher intraoperative blood product requirements and complicated intraoperative or postoperative courses increase the risk for IAI or DFI. The development of effective strategies to prevent CMV and fungal infections in liver transplant recipients remains a priority for future endeavors.

Topics: Bacterial Infections; Candidiasis; Cohort Studies; Cyclosporine; Cytomegalovirus; Cytomegalovirus Infections; Female; Graft Rejection; Humans; Liver Transplantation; Male; Middle Aged; Retrospective Studies; Risk Factors; Survival Analysis; Tacrolimus

Topics: Bacterial Infections; Diabetes Mellitus; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Pancreas Transplantation; Tacrolimus; Virus Diseases

Under FK506-based immunosuppression, 16 cadaveric small bowel transplantations were performed in 15 recipients with (n = 5) or without (n = 11) the large bowel. Twelve (80%) patients are alive after 1.5 to 19 months, 11 bearing their grafts, of which 4 include colon. The actuarial one-year patient and graft survivals are 87.5% and 65.9%, respectively. Five grafts were lost to acute (n = 4) or chronic (n = 1) rejection, and 3 of these patients subsequently died after 376, 440, and 776 days total survival. Six recipients developed severe CMV infection that was strongly associated with seronegative status preoperatively and receipt of grafts from CMV positive donors; 3 died, and the other 3 required prolonged hospitalization. Currently, 9 patients are free from TPN 1-18 months postoperatively, 2 require partial TPN, and one has returned to TPN after graft removal. The results show the feasibility of small bowel transplantation but emphasize the difficulty of managing these recipients not only early but long after their operation.

Topics: Adult; Bacterial Infections; Child; Child, Preschool; Colon; Female; Graft Rejection; Humans; Infant; Intestine, Small; Male; Middle Aged; Mycoses; Organ Transplantation; Postoperative Care; Tacrolimus; Virus Diseases

Topics: Adult; Bacterial Infections; Female; Follow-Up Studies; Graft Rejection; Humans; Intestine, Small; Male; Middle Aged; Mycoses; Postoperative Complications; Prednisone; Prospective Studies; Retrospective Studies; Tacrolimus; Time Factors; Virus Diseases

This prospective study characterizes the incidence, etiology, timing, risk factors, and outcome of the infectious complications after 88 consecutive liver transplantations in 79 patients receiving tacrolimus (FK506) as primary immunosuppression with a median follow-up of 880 days. Infections occurred in 59% (47/79) of the patients, and 39% had major infections. Of the major infections, 55% were bacterial, 22% were viral, and 22% were fungal. Bacteremia accounted for 30% of major bacterial infections. Sixty percent of bacteremias occurring within the first 3 months were catheter related, while 75% of those occurring more than 3 months after transplant were of a biliary source. Patients with recurrent hepatitis C virus hepatitis and patients requiring dialysis after transplant had a significantly higher rate of infections as compared with other patients. Overall mortality was 18%, and 29% of all deaths were associated with infection. Only invasive aspergillosis was associated with infectious mortality. Our data suggest that the potent immunosuppressive agent FK506 is not associated with a higher incidence of infectious complications as compared with previous studies using CsA.

Topics: Adult; Aged; Bacterial Infections; Female; Graft Survival; Humans; Immunosuppression Therapy; Incidence; Infections; Liver Transplantation; Male; Middle Aged; Mycoses; Postoperative Complications; Prospective Studies; Risk Factors; Survival Rate; Tacrolimus; Treatment Outcome; Virus Diseases

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Humans; Immunosuppressive Agents; Liver Transplantation; Mycoses; Opportunistic Infections; Risk Factors; Tacrolimus; Virus Diseases